Contemporary biomedical science has attempted
to explain behavior in terms of genetic determinism, with specific mental states
being produced by alterations in the brain concentrations of one or more
specific biochemical components. The literature relating to the presumed
association between low brain levels of the neurotransmitter serotonin and
aggression and suicide is reviewed and critiqued. Due to the variety of
methodological shortcomings in this research, conclusions based on the data
cannot be considered valid. Implications for the legal profession and for
Christian moral principles are discussed.

What Determines Behavior?

The debate about what molds human
behavior--nature versus nurture--has been with us for a long time. However, in
the last two decades or so, questions have intensified as an outpouring of new
discoveries in the neurosciences has become available. Whether the phenomenon is
called "sociobiology"1 (a term popularized
by E. O. Wilson) or the idea of "biological determinism" and the
"selfish gene"2 (a concept promoted by
Richard Dawkins), a growing body of scientific literature suggests that many
behaviors may be produced by changes in biochemical processes in the body. For
conditions ranging from depression through overeating to risk-taking and sexual
immorality, arguments are being made that we do these things as a result of our
individual genetic make-up and as a result of biochemical imbalances in the
brain.

In addition to issues of personal
responsibility and behavior, there is a growing interest in the legal profession
about questions dealing with neurochemical imbalances and legal liability for an
individual's actions. Over the years, several court cases have dealt with the
question of alcoholism and an individual's responsibility for his actions. A
review article in the Bulletin of the American Academy of Psychiatry and Law
focused specifically on information related to serotonin and behavior.3The writer called on forensic psychiatrists to be more aware of the current
neuroscience literature on how actions are influenced by biochemical changes so
that these findings could be incorporated into a better understanding of the
legal issues before the courts today.

For the Judaeo-Christian tradition, the
question is cast further in terms of individual responsibility, sin, and
accountability to God. If we are driven solely by biochemical processes over
which we have no control, then are we to be held accountable for our behavior?
Do the findings of modern science create a situation in which sin no longer
exists because we no longer are in control of our lives?

Given the variety of concerns that exist
about the relationship between biochemistry and behavior and the implications,
both legally and theologically, of current research in the field, a careful
examination of the professional literature is justified. Christians need to
evaluate the available information and to explore the consequences of accepting
conclusions based on this research. The focus of this paper is on the
relationship between serotonin and aggressive and suicidal behavior.

Serotonin Biochemistry

Structure and Function of Serotonin

Serotonin (5-hydroxytryptamine, 5-HT) is a
neurotransmitter that is formed from the amino acid tryptophan. This molecule
has a chemical structure similar to that of epinephrine (adrenaline) and
dopamine, both of which are known neurotransmitters. Interestingly, serotonin is
also structurally quite similar to the psychedelic drugs LSD, psilocybin, and
DMT (dimethyltryptamine), all three of which possess hallucinogenic properties.

The first studies on biochemical
properties of serotonin dealt with the effect of this compound in blood
pressure.4 When serotonin was first isolated from
blood in 1948, it was shown to promote constriction of blood vessels, increasing
blood pressure. Although platelets do not synthesize serotonin themselves, they
do pick up the molecules from the circulation. The molecule is also found in
high concentrations in the intestinal wall (where it is synthesized) and is
responsible for increased gastrointestinal mobility.

Biosynthesis and Metabolism

The amino acid tryptophan is the source of
serotonin in the body; approximately 1% of the total tryptophan pool is
converted to serotonin.5Tryptophan
initially undergoes conversion to 5-hydroxytryptophan, which then becomes
serotonin. Inactivation of serotonin is accomplished by the enzyme monoamine
oxidase, which also is involved in the inactivation of other neurotransmitters.
The inactivation product is 5-hydroxyindoleacetic acid (5-HIAA). In the pineal
gland, serotonin is changed to melatonin, a molecule involved in the regulation
of processes associated with the light-dark cycle (and implicated in such
phenomena as jet lag and seasonal affective disorder).

The major tissue site for serotonin
synthesis from tryptophan is the gastrointestinal tract. Other sites include the
thyroid gland, pancreas, and the thymus. These tissues are primarily responsible
for the serotonin detected in the blood. The brain synthesizes its own serotonin
from tryptophan which is able to cross the blood-brain barrier. Serotonin cannot
cross this barrier, so the body essentially has two separate pools of serotonin:
a blood-borne pool and a separate and distinct brain pool. The serotonin in the
brain cannot penetrate the blood-brain barrier to reach the general circulation,
and serotonin synthesized elsewhere in the body cannot enter the brain.
Measurements of serotonin and 5-HIAA in cerebrospinal fluid (CSF) are thought to
reflect the brain content of serotonin, since the CSF is formed in a portion of
the brain and then drains into the spinal column.

Serotonin as Neurotransmitter

The propagation of a nerve impulse by
serotonin is illustrated in Figure 1.6 Serotonin is
synthesized and stored in vesicles in the pre-synaptic region of the neuron.
When the nerve impulse moves down the fiber, it causes the release of serotonin
molecules, which then pass from the pre-synaptic membrane, cross the synapse,
and attach to specific receptors on the post-synaptic side. Interaction between
serotonin and the receptor then continues the nerve impulse further down the
fiber. Next, the serotonin dissociates from the receptor, is taken back up at
the pre-synaptic site, and is either inactivated by conversion to 5-HIAA or is
stored for reuse.

Where is serotonin located in the brain?
How much is there? These are difficult questions to answer. Although serotonin
neurons comprise only about 0.01% of the total number of neurons in the brain,
these relatively few cells are connected to an extensive network of nerve fibers
that extend throughout the entire brain. Serotonin nerve cells are clustered in
the base of the brain and interact intimately with other types of neurons
(mainly those stimulated by dopamine, epinephrine and norepinephrine). This
complex interplay among several neurotransmitters makes the task of elucidating
the specific behavior of serotonin and the influences this molecule exerts on
the nervous system a daunting task.7

Age and Gender Differences in Serotonin Content

The literature on reference values for
serotonin and 5-HIAA (normal values for age and gender) is sparse and confusing.
In general, the CSF concentrations of the serotonin metabolite 5-HIAA are lower
during middle age (35-55 years of age) than those seen in younger and older
populations.8This lower
concentration correlates with the lowered amount of the enzyme monoamine oxidase
(which converts serotonin to 5-HIAA) in the 35-55 year-old group. In addition,
the number of serotonin receptors (which transmit the effects of serotonin to
the nervous system) decreases with age in both men and women.

Significant gender differences exist in
serotonin production and conversion between men and women. The rate of brain
synthesis of serotonin in women is roughly half that in men.9
Some researchers have suggested that this lower rate of serotonin
formation is responsible for the much higher incidence of depression (3:1) and
eating disorders (10:1) in women than men. However, women have the same amounts
of the 5-HIAA metabolite, possibly due to higher concentrations of the enzyme
monoamine oxidase in the female brains. Women also have been shown to have a
lower number of serotonin receptors than men.10

Searching for Markers of Aggression and Suicide

A large body of research focuses on the
question of whether altered levels of serotonin in the body will precipitate
aggression or suicide. Benefits in identifying such a predictive biochemical
marker include both an improved understanding of these behaviors and possible
pharmaceutical intervention to prevent many incidents of violent behavior toward
others or oneself.

One positive outcome of this area of
research is the identification of specific areas of the brain where
abnormalities in serotonin synthesis, metabolism, or utilization occur. If there
are sites where the "cause" can be localized, this information may
suggest effective therapeutic interventions. An improved understanding of the
possible malfunction can lead to the development of safe and appropriate
pharmacological treatment. While these medications may not cure the problem (if
it is indeed a genetically determined disorder), greater control over behavior
can be achieved.

Christians involved in pastoral counseling
and hospital ministry need to be aware of this research. Some disorders (such as
schizophrenia and manic-depressive illness) apparently have a strong biological
basis for their causes. If these situations and current medical developments in
the field are understood, the ability to minister to patients and their families
and to communicate these issues and concerns to others in the congregation will
be enhanced. Pastoral counseling can be more effective in working with
individuals and in educating the body at large.

A large body of research focuses on the
question of whether altered levels of serotonin in the body will precipitate
aggression or suicide.

Some behavioral disorders apparently have
a biological cause and can be treated with good success. In many instances,
schizophrenia, which appears to have some common ground with aggression and
suicide, is very manageable with appropriate medication. Even though this
disorder (which appears to have a strong genetic component to it) cannot be
"cured" in the conventional sense of the word, individuals with
schizophrenia can lead productive lives when a proper drug regimen is followed
faithfully. Over 75% of persons with Cushings syndrome (due to a tumor on the
adrenal gland) experience profound depression because of excessive cortisol
production. In the vast majority of these patients, removal of the tumor leads
to an alleviation of the depressive state as the cortisol levels return to
normal. Although we do not yet understand all of the neurochemical issues
associated with bipolar depression (manic-depressive illness), the manic phase
has been successfully treated for decades with the use of lithium. A similar
beneficial outcome might be seen in individuals prone to violence or suicide if
a biochemical cause could be identified.

Much more problematic are the current
trends related to the explanation of behavior based on neurotransmitter
concentrations. On the one hand, we have extensive literature suggesting that
our genes are our destiny, that our behavior is determined by our biochemistry.
In other words, "it's not our fault." Current research can be
interpreted in such a way as to remove the idea of personal responsibility for
our actions. On the other hand is the reluctance on the part of some
constituencies to explore all aspects of the issue of violence. Research on
violence has been branded as racist because of concerns related to the use of
the data.11Certain ethnic groups and socioeconomic
classes fear further stereotyping (often with good reason) as a result of
investigations of violence in human society. Consequently, they strongly object
to all studies on the topic, fearing the outcome of the study before it is even
carried out.

What Parameters Are Studied?

Various approaches have been taken to
investigate the relationship(s) between serotonin concentrations in the body and
altered behavior. Many studies have been carried out using nonhuman organisms,
including crabs, mice, and monkeys. For many reasons, it is difficult to
extrapolate data and interpretations from animals to humans. Often metabolism,
enzyme properties, and behavioral influences are not the same when studies from
animal systems are extrapolated to humans. All of the information discussed in
this article will deal with data from human subjects.

Direct information has been obtained from
brain samples after death. Measurement of serotonin in these tissues gives some
indication of the status of the neurotransmitter at a specific point in time.
Information is not readily available concerning stability of tissue or
neurotransmitter concentrations after death. Nor is there any reliable data as
to the specific emotional state of the individual at the time of death. Many
studies do not have a good way to assess prior drug or alcohol use, parameters
that are known to influence serotonin concentrations.

In living subjects, serotonin metabolic
rates can be indirectly assessed using magnetic resonance imaging and positron
emission tomography (PET). The latter technique is an especially powerful tool
for monitoring changes in serotonin concentration during the course of an
experiment, providing real-time data on how rapidly this neurochemical is
utilized in specific situations.

A somewhat less direct assessment of
serotonin production by the brain has been employed in measuring cerebrospinal
fluid (CSF) levels of serotonin or (more commonly) the concentrations of the
metabolite 5-HIAA. The assumption is that CSF values correspond in some fashion
to the concentrations in the brain, since most CSF is produced in the choroid
plexus of the brain. The CSF circulates through various parts of the brain and
also drains into the spinal column. Although methods for detection of either
serotonin or 5-HIAA are fairly reliable, it is not clear how well the CSF
concentrations accurately reflect the biochemical processes taking place in the
brain itself. The average adult only has approximately 140 mL of cerebrospinal
fluid, which effectively eliminates the taking of a number of samples in
succession. In addition, the hazards associated with obtaining CSF samples
preclude serial testing, using multiple samples to obtain a dynamic picture of
changes that may be occurring over time.

Blood platelets have long been considered
to serve as a model for neurons affected by monoamines such as serotonin.
Platelets actively take up serotonin and store it in vesicles similar to those
in pre-synaptic neurons. This uptake can be blocked by drugs such as tricyclic
antidepressants. Several studies on the relationship between serotonin and
behavior have examined the number of serotonin uptake sites and the binding
properties of these sites in an attempt to gain a better understanding of
serotonin biochemistry in various disorders.

A few investigations have examined the
serotonin content of blood as a parameter that may affect the emotional state.
While concentrations can be reliably assayed using sophisticated immunoassay
techniques, the relationship between blood serotonin levels and brain
concentrations is questionable.

Serotonin and Violent Behavior

Any research into the root causes of
violent or aggressive behavior is fraught with pitfalls. Political agendas can
override the presumably dispassionate scientific objectivity of research. Groups
sometimes fear that the findings will be used inappropriately, to justify
discrimination or to focus undue attention on particular segments of the
population. In studies of the relationship between serotonin and aggressive
behavior, ethnic background has been ignored whenever possible, perhaps due to
the fear of creating unneeded controversy. Although some studies allow
identification of ethnicity (research on arsonists in Finland,12
genetic studies on an isolated Dutch family13),
race does not appear to be considered in research on violence.

Studies that relate serotonin and violence
draw from three sources: (1) CSF or other body fluid measurements from those
convicted of aggressive or violent behavior or those with a psychiatric problem
associated with this form of behavior; (2) tryptophan restriction studies to
explore how lowering of the precursor amino acid affects mood; and (3) studies
of persons with seasonal affective disorder (in which serotonin levels and
exposure to sunlight are linked).14

The most direct evidence for a link
between lowered serotonin and aggression comes from CSF studies of violent
individuals. These persons tend to have 5-HIAA values in the CSF that are
lowered when compared to a "normal" population. Not well documented,
however, is the relationship between low CSF levels of 5-HIAA (the metabolite)
and brain serotonin. Do low levels of 5-HIAA in the spinal fluid necessarily
correlate with low brain serotonin? In a previously mentioned Dutch family,15
the biochemical finding was a lowered level of monoamine oxidase, the
enzyme responsible for converting serotonin to 5-HIAA. In this situation, there
conceivably could be a normal (or elevated) brain serotonin content that is
simply not being metabolized to form 5-HIAA in the CSF. Other concerns about
these studies deal with the lack of reliable assessments of the tendency toward
violence. A numberof different measures are used, many of which do
not correlate well with other means of assessing the same parameter.

The most direct evidence for a link between lowered
serotonin and aggression comes from CSF studies of violent individuals.

Several studies have been carried out to
examine attempts to alter brain serotonin in presumably normal individuals.
Since no good pharmacological intervention exists to decrease brain serotonin
content, the strategy has been to reduce tryptophan intake in the diet. The
amino acid tryptophan is the precursor for brain serotonin; the assumption is
that lowering tryptophan consumption will lower production of brain serotonin.
While tryptophan restriction studies are more indirect, an increase in hostile
and aggressive attitudes is seen in those whose dietary intake of tryptophan is
decreased. However, these experiments have not directly demonstrated that
serotonin is the only brain component altered. Other presumably unknown factors
could play a significant role in the understanding of these data.

Even less conclusive are the arguments
that attribute increases in aggressive behavior to seasonal affective disorder
(SAD) and to presumed changes in serotonin concentration in the brain.16
SAD is considered to be a form of depression triggered by decreases in sunlight
and the resultant changes in melatonin production by the pineal gland in the
brain. While an increase in serotonin (produced by consumption of pasta or other
similar complex carbohydrates) can often alleviate many of the symptoms of SAD,
the major contributor to this form of depression is the melatonin cycle being
disrupted by the change in the amounts and timing of light and dark in the
environment. Apparently, multiple factors are involved in the depression and in
the resulting violence seen in individuals affected by SAD.

Serotonin and Suicide

In contrast to the limited data available
from subjects who exhibit aggressive or violent behavior, information from
individuals who commit suicide is more comprehensive.17
Analyses of both brain tissue and spinal fluid yield interesting, but
conflicting, information about the concentrations of serotonin and 5-HIAA in
these samples. A number of studies have shown a decline in either serotonin or
5-HIAA concentrations in brainstem samples from suicide victims. However,
measurements of these compounds in another area of the brain (the frontal
cortex) suggest that no significant difference exists between serotonin or
5-HIAA concentrations in those individuals who committed suicide and in victims
of accidents or other non-neurological fatalities. In addition, studies of
5-HIAA levels in CSF of persons who had attempted suicide show a mixed and
inconsistent collection of results--some papers report decreases in values,
others report essentially no differences in values.

Complications in the analysis of data in
serotonin and suicide are many. Usually, no history of drug use, especially
long-term involvement, is readily available. Some of the common modes of suicide
(drug overdose and carbon monoxide poisoning) have not been evaluated in terms
of the changes in brain chemistry that could be produced by the drug or by
carbon monoxide. Brain tissue stability after death, time between death and
autopsy, accuracy in removing and identifying the locale of brain samples, diet,
and time of year are all parameters that will affect serotonin and 5-HIAA levels
in the brain. These parameters have not been carefully controlled in the vast
majority of the reported studies.

As is noted in the next section, decreases
in CSF serotonin and/or 5-HIAA have often been reported in patients diagnosed
with clinical depression. Many papers, looking at a possible link between low
serotonin and suicide, examine depressed patients with suicidal behavior.
Therefore, conclusions reached for suicidal patients must be considered even
more questionable, since two variables (depression and suicide) are being
mingled together in the data analysis.

Serotonin and Depression

Investigations of possible relationships
between altered serotonin biochemistry and depression are of particular
importance because of the possibility of manipulating these levels with drugs in
an attempt to treat the depression.18 The original
hypothesis of lowered serotonin levels resulting in clinical depression has not
been well substantiated. Studies show mixed results, with some researchers
reporting decreased 5-HIAA values in the CSF of depressed individuals, while
others observe no difference in values between patients with depression and the
control population. Tryptophan depletion in the diet can induce depression in
some normal individuals (presumably due to the diminished availability of
tryptophan for brain synthesis of serotonin), but gives variable results in
patients who are already depressed.19As previously noted, these studies do not demonstrate directly a decrease in
brain serotonin; the presumed lowering is inferred from the dietary restriction
on tryptophan. However, as we see in the next section, pharmacological
manipulation of serotonin levels is widely used in modern-day psychiatric
treatment for depression.

Furthermore, most studies do not provide
clear boundaries that distinguish the types of individuals seen in the research.
Patients are often suicidal and depressed, depressed and schizophrenic,
schizophrenic and violent, violent and alcoholic, or any combination of the
above. A well-defined patient population with only a single psychological issue
does not appear to be available for study.

Prozac, Other SSRIs, and Serotonin

As the need for more effective
antidepressants became obvious in the late 1960s, research began on a class of
drugs known today as selective serotonin re-uptake inhibitors (SSRI).20
Prozac (fluoxetine) is probably the best-known product of this class of drugs.
These inhibitors work primarily by blocking the ability of the pre-synaptic
neuron to "reabsorb" serotonin after the molecule has interacted with
the post-synaptic serotonin receptor to continue propagation of the nerve
impulse (see Fig. 1, step 5). The net result is a prolonged exposure of the
post-synaptic receptor to serotonin, effectively increasing the concentration of
serotonin at that site. The rationale behind the use of SSRIs is that the
elevated amount of serotonin at the synapse presumably alleviates some of the
behavioral symptoms believed to be associated with low serotonin levels.

Prozac (first prescribed in the U.S. in
1988) and its companions appear to be better tolerated than the tricyclic
antidepressants they are replacing, whose side-effects include dryness of mouth,
sedation, and low blood pressure. The SSRIs appear to be more effective in
treating depression than other classes of antidepressants, presumably due to the
increase in serotonin at the post-synapse produced by this class of drugs.

The results of research on the use of
SSRIs to modify suicidal or aggressive behavior are mixed.21Few studies have been carried out to date. No large patient populations
have been investigated. Treatment results are not consistent, since some
patients show positive change while others demonstrate no improvement in
behavior. Several investigations raise the possibility that SSRIs induce an
increase in suicidal ideation among some patients,22
a behavior directly contrary to that predicted by the prevailing paradigm. If a
true causal relationship between lowered synaptic serotonin and these behaviors
existed, a more consistent relationship between SSRI use and alleviation of
aggressive or suicidal tendencies would be expected. However, this relationship
appears to be either weak or non-existent.

Problems with Studies on Serotonin and Behavior

At first glance, it might appear that the
available data support the idea that low brain serotonin will produce changes in
behavior that have a high probability of leading to aggression, violence, or
suicide. However, a closer examination of the studies raises some significant
methodological questions.

Inconsistencies among Studies

One concern is the inconsistent data
obtained from the various research studies. Attempts to affect the brain supply
of serotonin by either depleting or increasing body tryptophan loads provide
mixed results in terms of the observed behavior. Some studies show the predicted
effect, while others do not. Measurements of receptor numbers and binding
affinity for serotonin are plagued by the fact that there are at least thirteen
known serotonin receptors in humans, with little known about exactly which
receptor mediates which neurochemical process.23The rate of serotonin synthesis in the brains of women is much lower than
for men, an observation used to explain the higher incidence of depression (and
suicide?) in women. However, fewer aggressive acts are committed by women, a
fact that is inconsistent with their presumed lower brain serotonin content.
While SSRIs are used to increase brain serotonin content to alleviate aggressive
and suicidal tendencies, a review of the literature shows mixed and
contradictory results obtained from the use of Prozac and related drugs. Recent
newspaper articles indicate that the pharmaceutical company which manufactures
Prozac suppressed evidence that the drug produced suicidal behavior in a number
of patients taking it, raising further questions about proposed links between
low serotonin concentrations and suicide.24

Methodological Shortcomings

A variety of methodological problems
plague the research findings that attempt to link decreased amounts of serotonin
with behavioral change. I will simply list them briefly:

1. The amount of 5-HIAA in the CSF does
not necessarily correlate with the concentration of serotonin in the brain.

2. Platelet studies are not a good
indicator of serotonin activity or concentration in the brain. Similarity of
biochemical properties does not imply similarity of neurotransmitter
concentration or receptor number.

3. Many studies did not take into account
the recent findings dealing with gender differences in the amount of serotonin
in the brain.

4. Serotonin receptor populations in the
brain are poorly characterized, in terms of both the number of receptors and the
specific sub-types of serotonin receptors.

5. "Cross-talk" among different
neurotransmitters and receptors is poorly characterized at present. We know that
serotonin can produce some activation of dopamine and epinephrine receptors, and
these other neurotransmitters can stimulate serotonin receptors, although the
extent of these cross-interactions is not clear. Therefore, we must look at
concentrations of at least three different neurotransmitters simultaneously.
Little data exist dealing with this question.

6. Information about prior drug use
(either prescription medications or illicit drugs) is often not available or is
unreliable. We learned the hard way from earlier research on schizophrenia that
certain drugs can drastically alter the number and behavior of specific
receptors. Further research into the effects of drugs on serotonin
neurochemistry is definitely needed.

7. The effect of sampling technique on the
values obtained for the neurotransmitter and metabolites has not been thoroughly
explored. One recent paper indicates that CSF samples collected soon after the
lumbar puncture procedure yield 5-HIAA values about 54% of those were obtained
several hours later, after the sampling apparatus was in place.25The stress of the sampling procedure was thought to have produced the
initial decrease in metabolite concentration. Most (if not all) of the studies
conducted on living patients utilized CSF samples collected immediately upon
puncture. The lower values thus obtained could well have been due to the stress
of the situation and not the underlying psychological condition. This factor
needs further exploration and validation.

Recent findings about serotonin and stress open some
interesting doors to the impact of emotions on brain biochemical processes and
later behavioral states.

8. No longitudinal studies exist to
explore whether the serotonin levels decrease over time as the psychiatric
problem worsens (to show that the increasingly aberrant behavior is produced by
the decline in neurotransmitter concentration). In addition, no studies show
that individuals who have low serotonin levels early in life are more likely to
be overtly violent or suicidal later. While some significant ethical problems
are involved in carrying out this type of research, the information is
definitely needed to substantiate the present paradigm.

9. Information is becoming available which
could suggest that psychological stress can contribute to a decrease in
serotonin concentration,26and be
the precipitating agent in aggressive or suicidal behavior. Therefore, the
change in the amount of brain or CSF serotonin would be the result of altered
psychology, and not the other way around.

The idea that psychological stress can
alter biochemical production in humans is well documented. We are all familiar
with the surge of energy, the increase in heart rate and respiration, and the
heightened awareness that comes when we are suddenly frightened. A major
contributor to these responses is the increase in catecholamines (such as
adrenaline) in response to a sudden stress. The same increase can come over a
longer period of time, when the stress is not so apparent (as has been
documented with students taking an exam). Prolonged increase in catecholamine
concentrations can have profound effects upon other biochemical functions in the
body.

Another hormone response to stress is
cortisol, a steroid hormone. Disturbances in both the total daily output of
cortisol and in its diurnal rhythm can be produced by emotional stress (either
short-term or long-term). Emotional stress causes an increase in the amount of
cortisol and a tendency for the diurnal cycle to disappear. The loss of the
diurnal cycle results in the elevation of cortisol levels throughout an entire
twenty-four hour period, instead of decreasing at night. Alterations in both
cortisol and catecholamine metabolism are both affected significantly by stress.27

The role of stress in mediating serotonin
output is confusing, but intriguing. Not only does stress affect the release of
serotonin, but also an intricate interplay between serotonin levels and the
regulation of systems leads to the production of catecholamines and cortisol,
among other hormones.28 Coupled with the widespread
speculation that long- term stress can produce altered brain function
(especially in small children), these recent findings about serotonin and stress
open some interesting doors to the impact of emotions on brain biochemical
processes and later behavioral states.

Sensitivity, Specificity, and Serotonin

One key test for the utility of a
diagnostic marker is its sensitivity and specificity.29
Any test used to assist in the diagnosis of a disease must successfully identify
those individuals who have the disease while reliably excluding those who do not
have the disease. Ideally, there is no overlap between these two populations,
but in real life this is not possible. There will usually be some overlap
between the two groups. Two ideas are used to assess the diagnostic utility of
laboratory data: sensitivity and specificity. "Sensitivity" describes
the "incidence of true- positive results obtained when a test is applied to
patients known to have the disease." This number indicates how well the lab
test allows detection of patients with the disorder under consideration.
"Specificity" is used to "characterize the incidence of
true-negative results obtained when a test is applied to subjects known to be
free of the disease." Therefore, if a lab test has 100% sensitivity, it
will provide abnormal results for all of those individuals who have a certain
disease. A lab test that shows 100% specificity gives normal results for 100% of
the population who do not have the disease. False- positive results (an abnormal
value in a person who does not have the disorder) and false-negative results (a
normal value in a person who does have the disorder) lower the predictive value
of the test.

Using these concepts, we see that low
serotonin values are not predictive for a certain type of behavior (i.e.,
suicide or violence). Two flaws appear in the literature. First, there are no
good reference values to be used for comparison purposes. As pointed out
earlier, population studies are few and comparison groups are sparse.
Methodological problems mar most of the studies. Perhaps more telling is the
range of conditions for which low serotonin or HIAA values have been reported.
These psychological problems include alcoholism, obsessive- compulsive disorder,
schizophrenia, Alzheimer's disease, anorexia/bulimia, panic disorder, anxiety,
pre-menstrual syndrome, migraine, and autism.30
Clearly, these disorders represent a wide variety of psychological and/or
neurological problems. The association of low serotonin levels with each of
these disorders may be more a reflection of some underlying psychological state
that produces the altered neurotransmitter concentration than some unified
effect of lowered serotonin values on this myriad of behaviors.

One interesting wrinkle in this area of
"behavioral biochemistry" is the repeated finding that low serum
cholesterol values are associated with an increased incidence of aggressive
behavior.31 Are there biochemical links between the
amount of cholesterol synthesized and brain production of serotonin?
Increasingly, we are seeing reports of a relationship between the amounts of
certain steroid hormones (all of which have cholesterol as the precursor
molecule) and changes in serotonin metabolism. These data provide just one small
hint that our understanding of the connections between our biochemical selves
and our behavioral selves is extremely limited.

Implications of Research on Serotonin and Behavior

Scientists who study factors that
determine behavior will readily concede that a specific behavior is influenced
by both environmental and genetic determinants. However, the studies considered
in this paper attribute (directly or often by implication) the abnormal behavior
to changes in the concentration of a specific neurotransmitter. In most primary
research publications, the investigators simply indicate "an association
with" or "a correlation between" low serotonin activity and
behavior, but offer no mechanism of action or cause-effect relationship. Yet, a
strong thread runs through both research publications and more popular science
articles to involve diminished serotonin content in the brain as a precipitating
agent for violent behavior. Here is a selection of quotes from the research
literature on serotonin and suicide:

To our knowledge, this is the first
report to implicate a specific gene in the predisposition of a behavior (suicidality)
postulated to be regulated by serotonin.33

The link between serotonin functions and
suicidal behavior might be a deficient control of aggressive impulses.34

The more "popular" science
literature and reports in newspapers and news magazines also clearly state the
belief that low serotonin is the cause of suicidal behavior:

Some studies ... already have hinted
that distinctive biological mechanisms might be responsible for suicidal
behavior.35

This predisposes a person to act on
suicide thoughts ... Serotonin is important for restraint. If serotonin is
reduced, a person is more apt to act on powerful feelings.36

A mutant gene that affects brain
chemistry in unknown ways may drive some depressed people to kill themselves,
say Canadian psychiatric researchers.37

Although these quotes deal specifically
with serotonin and suicide, equivalent thinking can be documented for other
issues associated with low serotonin.

The overall mechanism usually suggested
(when one is proposed) is that serotonin is an inhibitory neurotransmitter in
the central nervous system, modulating impulse control. Decreased brain
concentrations of serotonin are believed to release the brain from this control,
which then allows the person to act out a variety of behaviors, especially
aggressive or violent actions. If this is true, then behavior (to some extent)
is determined by factors outside our control. If we cannot control our behavior,
then (by implication) we are not responsible for that behavior. There is a
growing assumption in some of the medical literature, and certainly in the
popular press, that we cannot be held accountable for many of our actions.
Alcoholics are treated as if their condition were caused (at least in part) by
some defective gene that gives rise to the excessive consumption of alcohol,
even though every study that claims to demonstrate the presence of a gene for
alcoholism has quickly been refuted. The destructive behavior that often
accompanies depression is attributed to a "chemical imbalance."

There is a growing assumption in some of the
medical literature, and certainly in the popular press, that we cannot be held
accountable for many of our actions.

This line of thinking is being translated
into legal considerations. In both British38 and
American39law journals, the
legal implications of current research on biochemistry and behavior have been
discussed. While the Bradford (American) article is primarily a survey of the
scientific literature, the Fenwick (British) article considers some of the legal
implications of violent acts committed while under the influence of a disease or
temporary abnormal brain function. The conclusion of both authors is that
demonstration of altered neurochemistry can successfully be used in court as a
mitigating circumstance, which could lead to either a reduced sentence or
acquittal.

One such case involved Tony Mobley, who
had a history of violent behavior. During his 1995 trial for murder, his
attorneys argued that he was not responsible for his behavior and that it was
possibly due to serotonin deficiency.40 Although
the judge agreed that this possibility might exist, he denied the request of the
defense to have Mobley tested and to have the results admitted in court. Mobley
was found guilty and the attorney filed an appeal based in part on the judge's
refusal to admit test data into evidence.

If aggressive or suicidal behavior is due
to a serotonin imbalance, the logical next step is to attempt to correct that
imbalance by way of pharmacology. Administration of Prozac or other serotonin-selective
re-uptake inhibitors has been extensively used as treatment for these states
(not always successfully). The presumed success of these pharmacological
approaches provides the "easy" solution, but does not deal with the
root cause of the behavior. Our society continues to become even more a society
that solves its problems by taking a pill.

Some ethnic minorities have expressed
grave concern about the implications of research on violence and often have
actively opposed studies exploring the causes of this behavior. If violence is
clearly linked to a serotonin imbalance, and if that serotonin imbalance is
genetically determined (which has not been demonstrated to date), then it
follows that the incidence of violence could be reduced by limiting reproduction
of the defective gene. Earlier efforts to control the further development of
sickle-cell disease (an abnormality of hemoglobin structure that primarily
affects individuals of African descent) led to accusations of "genetic
cleansing" by some segments of the population. The eugenics movement of the
early twentieth century in the Unites States and elsewhere and the efforts of
Hitler to eliminate "defective populations" are reminders of the
persecution that can be visited upon minority populations under the guise of a
greater social good.

What Does This Mean for Christians?

Dean Hamer in Living with Our Genes
(Doubleday, 1998) argues that genes are a major influence on our personalities
and behaviors. In her book, The Biologyof Violence (Free
Press, 1999), Debra Niehoff explores the relationship between brain chemistry
and behavior, concluding that our behavior is based to a great extent on
neurobiological processes. In the April 1998 issue of Atlantic Monthly,
E. O. Wilson argues that religion and ethics "can all eventually be
explained as functions of brain circuitry and deep genetic history." An
April 21, 1997 article in U.S. News and World Report states: "For
both political and scientific reasons--and it's often impossible to disentangle
the two--everything from criminality to addictive disorders to sexual
orientation is seen today less as a matter of choice than of genetic
destiny." Eric Kandel, M.D., of the Center for Neurobiology and Behavior at
Columbia University, recently issued a challenge to his colleagues in the
psychiatric field when he proposed that biology was central to the future of
psychoanalysis.41 Kandel indicated several areas
where biology would provide the definitive answers to issues in behavior
(psychopathology) and sexual orientation.

Admittedly, there is more to the above
picture, although the extent of the "more" is being strongly debated.
Environment certainly plays a role, but the question is that of extent. Nurture
and nature are intimately intertwined, with nurture often having a lasting
impact upon nature--early childhood stress and abuse, for example, appear to
produce lasting changes in brain structure and chemistry. But the questions
remain: Is behavior determined by our biochemistry or by our moral sense? Are we
responsible for what we do or can we blame it on our biology, our genes, and
then not be held accountable for the consequences?

The issues raised in this paper are but
one component of a discipline known as evolutionary psychology. This field of
study explores the way we behave as being expressed through our genetic make-up.
Just as Darwin and his successors have given us a world in which the physical
realm appears to be all there is, evolutionary psychology tries to provide
explanations for our behavior in terms of biology. However, this field presents
not just a scientific endeavor, but also a philosophical commitment. This
component of the field was best explained by Charles Colson and Nancy Pearcey in
a Christianity Today column (August 10, 1998):

Some Christians have hoped to make peace
with Darwinism as long as it is restricted to biology. But evolutionary
psychology demonstrates that there is an inexpungable imperialism in
Darwinism--a compulsion to reduce all society to material mechanisms. Just as
Darwinist theory in biology aims to replace divine design with natural
processes, so in ethics it aims to replace revealed morality with a
naturalistic morality. Sociologist Howard Kaye observes evolutionary
psychology is nothing less than a secularized natural theology--an attempt to
justify a secular world view.

As Christians, we represent a
counterculture to the norms of secular society. We are led, on the basis of
Scripture, to conclude that each person is accountable for his or her behavior.
When the broader society offers the message of biological determinism, we have a
responsibility to challenge that paradigm. Moreover, we are called to proclaim
truth, whether that is truth of the Bible or a truth that goes against the
secular world.

Investigation of the research linking low
serotonin levels to violent or suicidal behavior suggests that the basic
conclusions can be successfully challenged. The research obviously is incomplete
(as most workers in the field readily acknowledge). The role of stress as the
initiating factor in altering brain serotonin concentrations and later behavior
appears to have strong support from the empirical data. Relationships between
serotonin content and aberrant behavior are being proposed without a thorough
consideration of all of the parameters involved. Much of the research has not
been evaluated according to criteria used to assess whether or not a particular
biochemical marker is a true indicator of a specific disease. Those criteria
seem to indicate that low brain serotonin is a nonspecific phenomenon associated
with a variety of situations that have no apparent common denominator other than
stress.

As our knowledge of neurotransmitter
biochemistry increases, we need to include that new knowledge in the
interpretation of data. There is a growing awareness of the interconnections
between mind and body--our emotional state can profoundly influence the
concentrations of specific biochemicals just as the changes in the amount of
certain materials can have an influence on our mood and behavior. We cannot
assume a one-way link between biochemistry and behavior.

As Christians, we represent a counterculture to the norms
of secular society. We are led, on the basis of Scripture, to conclude that each
person is accountable for his or her behavior.

We intuitively believe that we are more
than a simple collection of chemicals and therefore are responsible for our
behavior. Increasingly, we are able to challenge the naturalistic paradigm not
only with reason, but with hard data. A careful review of the literature,
challenging the assumptions and methodologies of the studies cited above, allows
us both to do good science and to establish more firmly the idea of personal
moral responsibility. In a broader context, the philosophy that underlies much
of evolutionary psychology must be seen for what it is--an attempt to dethrone
revealed moral law and replace it with an ethical and political philosophy that
frequently serves only as a rationalization for giving in to our basest desires.

As Christians and as scientists, we have a
unique role to play in the societal debates that take place around us. Too often
believers are asked to alter or abandon fundamental Christian beliefs and
practices because science has supposedly shown them to be incorrect in some way.
If we believe that God is a God of truth, then the claims of the secular society
need to be evaluated and challenged when they contradict the revelation we have
received. Those claims just may turn out to be wrong.

39J. M. W.
Bradford, "The Role of Serotonin in the Future of Forensic
Psychiatry."

40M. Curriden,
"Guilt by Heredity? His Lawyer Says It's in the Killer's Genes," The
National Law Journal (November 7, 1994): A12.

41E. R. Kandel,
"Biology and the Future of Psychoanalysis: A New Intellectual Framework for
Psychiatry Revisited," American Journal of Psychiatry 156 (1999):
505-24.

Donald F. Calbreath is currently an associate professor of
chemistry at Whitworth College (Spokane, WA) where he has taught for seventeen
years. He received a B.S. in Chemistry from North Texas State University in 1963
and a Ph.D. in biochemistry from Ohio State University in 1968. From 1968-1970,
he did post-doctoral research in the Biochemistry Department at Duke University.
Then he directed a clinical chemistry laboratory for Durham County General
Hospital in Durham, NC, and taught laboratory medicine as an adjunct faculty
member in the Duke University Medical School program for physicians assistants.
He has had a longstanding interest in biochemical aspects of mental illness and
the relationship between biochemistry and behavior. The current research was
funded by a Pew summer research grant and an award from the faculty research
grant program at Whitworth. In his spare time, Calbreath is a devotee of
traditional Southern music and (along with his wife Sandy) enjoys spoiling his
three grandchildren.